Abstract
Trichomonas vaginalis is a causative agent of Trichomoniasis, a leading non-viral sexually transmitted disease worldwide. In the current study, we show Heat shock protein 90 is essential for its growth. Upon genomic analysis of the parasite, it was found to possess seven ORFs which could potentially encode Hsp90 isoforms. We identified a cytosolic Hsp90 homolog, four homologs which can align to truncated cytosolic Hsp90 gene products along with two Grp94 homologs (ER isoform of Hsp90). However, both Grp94 orthologs lacked an ER retention motif. In cancer cells, it is very well established that Hsp90 is secreted and regulates key clients involved in metastases, migration, and invasion. Since Trichomonas Grp94 lacks ER retention motif, we examined the possibility of its secretion. By using cell biology and biochemical approaches we show that the Grp94 isoform of Hsp90 is secreted by the parasite by the classical ER-Golgi pathway. This is the first report of a genome encoded secreted Hsp90 in a clinically important parasitic protozoan.
Highlights
Trichomonas vaginalis is the causative agent of Trichomoniasis, a leading non-viral sexually transmitted disease worldwide [1]
Hsp90 is an essential chaperone in eukaryotes and it is often described as a master regulator of cellular homeostasis
Our analysis of Grp94 sequences from protozoa shows that it is uncommon for a Grp94 to lack ER retention signal
Summary
Trichomonas vaginalis is the causative agent of Trichomoniasis, a leading non-viral sexually transmitted disease worldwide [1]. Secreted Hsp in T. vaginalis genitourinary tract, can be involved in premature labor and low birth weight. Epidemiological studies show a two to three-fold increase in the risk of HIV infection in people with Trichomoniasis due to HIV target cells, CD4+ T-lymphocytes, recruitment at the site of infection [2, 3]. This parasite infects more than 270 million people worldwide annually, despite which there is no clear consensus on its pathogenicity mechanisms. Due to the synergy with HIV infection and increase in reports of drug resistance, it is pivotal to understand the basic survival principles of the parasite [2, 4]
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